The goal of this SCORE renewal application is to identify and characterize key risk factors for thrombosis that will improve methods for its prevention and treatment. The SCOR is specifically designed to promote synergy between basic and clinical research. The SCOR is specifically designed to promote synergy between basic and clinical research. It includes randomized clinical trials to address optimal anticoagulant therapy for venous thrombosis (Project 1), biochemical projects that examine the membrane requirements for activated protein C function (Project 2), the structural requirements for the cofactor and signaling functions of the endothelial protein C receptor, the membrane requirements of the tissue factor/factor VIIa complex, and the use of gene-targeted mice to study the functions of vascular adhesion and signaling molecules in vivo. There is scientific overlap in the scientific goals of the laboratory-based projects. In addition, an essential link for all SCOR components is the Assay Core, which performs coagulation, ELISA, and DNA assays on blood samples from the patients in Project 1. The data from these assays will help answer mechanistic questions in the laboratory-oriented projects, which in turn, will help to define specific risk factors for thrombosis in the patients of Project 1. The SCOR is organized to facilitate generation and testing of hypotheses that will move between the basic and clinical arenas. The long-term objective is to better understand the etiology of thrombosis, thereby allowing design of better treatment strategies.